Compounds of this type, preferably N-methyl amino acids, are e.g. components of cyclosporins. Cyclic peptides are involved which exhibit antibiotic and immunosuppressive action and for this reason are frequently used in tissue transplantations.
Racemates of these compounds can generally be produced in a purely chemical manner. However, the separation of these racemates into the individual enantiomers is very expensive and requires, e.g., chiral chromatographic columns. A further method of producing these enantiomerically pure compounds is via the free L- or D-amino acids, which are then subsequently alkylated to the .alpha.-amino group and optionally acylated.
However, a large number of byproducts is produced in this process which considerably reduce the yield and can often be removed only with great expense.
An enzymatic production of these compounds, e.g. by means of acylase, always has been unsuccessful in the past due to the unduly narrow substrate specificity of the acylases used. Acylase I is suitable, as described in The Journal of the American Chemical Society, 75, 918-920 (1953) and 111, 6354 to 6364 (1989), for the resolution of racemates of acylated .alpha.-amino acids insofar as the latter have a free hydrogen atom in the acylated amino group. The splitting then takes place L-specifically, so that the N-acyl-D-amino acid remains unsplit and can be separated, e.g., chromatographically or by means of precipitation from the L-amino acid produced: Acylase I, which can be isolated, e.g., from hog kidney or from Aspergillus, does exhibit a broad substrate specificity but no activity at all in the case of N-acyl-N-alkyl-DL-amino acids. Recently, other acylases have been found which have a specificity for terminal proline in peptides and to N-acyl proline as well as to cyclic N-acylatedamino acids modified from proline. These newer acylases are described in Japanese Patent Application 62-232381 (1987), "Biochimica et Biophysica Acta", 744 (1983, pp. 180-188 and in Published European Patent Application EP 0 416 282 A1. A substrate specificity to open-chain N-acyl-N-alkyl amino acids is not known for these acylases.